Is industry best practice in DTC genetics good enough?

(It looks like this has become Regulation Week here on Genomes Unzipped; Daniel’s initial post sparked a ferocious comments thread, and follow-up posts from Caroline, Dan V and Jeff and Kate continue to add fuel to the discussion. We have one more post on regulation to come to round off the week, before next week returning to our regular, more balanced schedule of posts.)

It’s becoming clear that the arguments with regards to direct-to-consumer (DTC) genetics here aren’t really about regulation per se; I doubt anyone wants to see companies be allowed to make any claims they wish without requiring accuracy or consumer protection. So what exactly are we arguing about?

There are a set of arguments that essentially come down to how one trusts the FDA to act rationally and in everyone’s best interests: some people point to recent statements from FDA officials as evidence that they will apply overly strict regulation, or regulation that requires implausible amounts of money and effort to comply with; others point to the American government’s strong tradition of supporting business, and assume that cooler heads will prevail when it actually comes to making policy. These are arguments about the FDA specifically, and the American legal and legislative system in general, that only one of the Genomes Unzipped contributors has a strong background in.

Beyond specific questions about the actions of the FDA, discussions in the comments here and elsewhere appear have brough up two differing viewpoints about what DTC regulation should look like. One viewpoint (e.g. Daniel MacArthur’s) proposes a Trade Standards/consumer protection type regulatory mechanism; ensuring technical accuracy, associations and health claims based on well-supported scientific evidence, and a lack of misleading or confusing claims or presentation. The other suggests that we need to go further, and proposes something more akin to the regulation of medical practice; some combination of proven clinical utility, proven lack of significant clinical harm, direct supervision by a trained medical professional and high standards of informed consent.

To put it another way, the first viewpoint suggests that industry best practice, embodied by 23andMe’s white papers, deCODEme’s Code of Conduct, and the transparency afforded by the Genetic Testing Registry grants sufficient protection for the public. The role of regulation should be to distill these best practices into legal guidelines, which companies that stray from can be prosecuted for. Any more regulation, and we intefere with the right of individuals to access and engage with their own genetic information, any less and we allow them to be taken advantage of.

The second viewpoint implies fatal flaws in existing best practice, and that by making medical claims the DTC genetic testing industry have attempted to take on the mantle of medical professionals. Carrier testing, BRCA screening and breakdowns of actionable health risks are the purview of clinical geneticists, with the extensive training, vetting and oversight doctors are subject to; if DTC genetics companies want to share this turf, they should be subject at least some of the same requirements.

My aim in this post isn’t to come to a conclusion on which approach is correct; I seem to have convinced myself of both views sequentially while writing it. From my point of view, the series of posts and the diverse comments they have inspired have helped me clarify in my mind, if not what I think is the right approach, at least what questions need to be asked to lead us to the right approach.

Tomorrow we will have our last regulation post (for the moment) by Dan Vorhaus, summarising the various issues that have been raised, and the key questions we need to think about as we move forward.

The second approach would be utter folly. Taken to its logical end, it has the potential to close down all genetic research with medical implications within the US, not just the presentation of the results via DTC companies, or research with medical implications using the database provided by DTC customers (such as that on Parkinson’s Disease by 23andMe).

Researchers with degrees in biology and/or genetics, but not medical degrees, are constantly publishing genetic research with medical implications. In other words they are making available to the public knowledge which any individual who has access to his or her own genomic data can apply to him or herself. Where are regulators going to stop in that case? Prevent publication without a medical degree? Ban all genetic testing of US citizens?

Given this ongoing discussion it seems to me that the most useful thing GenomesUnzipped could do is write a future post that would attempt to define what is “medical genetics” and what is only “genetics”.

The point is that medical genetic testing is already regulated. It’s called CLIA/CAP. The only question at hand is whether MORE regulation of the multimillion dollar kind is necessary.

In this whole discussion the word “BRCA” may have come up 20 times. But the fact that Myriad’s BRCAnalysis test is an LDT under CLIA/CAP, not FDA has not come up at all. Whatever you may think of their business practices, Myriad built a multibillion dollar public company that is the standard for BRCA testing. No one is saying that their test is of poor quality.

…By the way, as a tangent regarding Myriad, if you want fewer gene patents you do not want the FDA involved. The trade they have made with drug companies is to massively increase the frontend capital costs ($500M or more to get a drug through) while acting as enforcers of drug patents. This is why the developing world HATES the FDA, because they see them as the protectors of rich nation’s property rights.

And it gets weirder. Once a drug patent expires, the FDA grants a 180 day monopoly to a generic manufacturer, like Ranbaxy. This is supposed to compensate them for the risk of being sued by the patent holder!

This sounds crazy, and it is. It causes all kinds of bizarre market distortions. As one consequence, the original drug manufacturer often pays off the generic developers to not bring their products to market, to extend their effective period of exclusivity.

The whole thing is screwed up, but one thing is for sure: if every genetic test has to pass through the multimillion dollar FDA process, there will be a strong push to re-establish property rights over the genome through the mechanism of gene patents, just as there was with drug patents.

(Name of applicant) was the first applicant to submit a substantially complete ANDA with a paragraph IV certification. Although you were not sued as a result of the notice you provided to the holder of the NDA and the patent owner, you are nonetheless eligible for 180 days of market exclusivity. Such exclusivity will begin to run either from the date you begin commercial marketing or from the date of a decision of a court finding the patent invalid or not infringed, whichever is earlier (section 505(j)(5)(B)(iv)). A court decision that can trigger the beginning of exclusivity is a decision of any court in a patent infringement action resulting from a paragraph IV certification in which the court finds that the patent is invalid or not infringed. In a case such as yours, where the first applicant is not sued for patent infringement, the court decision would obviously be rendered in a case involving a subsequent ANDA applicant. With respect to the “first commercial marketing” trigger for the commencement of exclusivity, we draw your attention to 21 CFR 314.107(c)(3) and (4). The Agency expects that you will begin commercial marketing of your product promptly upon approval.

I agree with Caroline: what constitutes “medical” and who makes that determination? What is “predicting disease?” Consider APOE: it plays a role in Alzheimer’s, cardiovascular disease and macular degeneration. In AD it is clearly important; in the other two, less so. Are we going to apply different regulatory standards to different predictions attached to the same alleles? I don’t see how.

Now suppose it’s even more complicated: what if APOE were part of a chromosome-19 haplotype that was highly predictive or even “diagnostic” of a particular ancestry? Does 23andMe redact it? What about Oxford Ancestors and Family Tree DNA and every population genomics research endeavor?

No-one is ever going to regulate your right to read a pile of biomedical journals and text-books and draw conclusions about your own health from them. However, anyone who says that they will read these for you, and come to conclusions about your health, in return for money, needs to some form of regulation. The debate is only over whether reading a particular field of medical literature, and applying it to a particular individual, is a consumer or a medical service, and thus whether it requires consumer protection or medical test regulation.

Luke – the dichotomy between consumer protection and medical device regulation is a false one. FDA is in the business of consumer protection, not least through its regulation of OTC pharmaceuticals and medical devices.

Nobody has so far mentioned that there is apparently a draft bill in the US which, if approved, would create a new “Center for Advanced Diagnostics Evaluation and Research that would be responsible for evaluating a new category of tests called “advanced personalized diagnostics,” a term comprising genetic test kits and laboratory-developed tests.”:

There is some excellent coverage in today’s Times by Mark Henderson on the problems with the population risk data reported by the DTC genetics companies. The three companies concerned have all commendably responded to the concerns and are addressing the issues. You can read the stories here but you will need to pay a fee (I think it’s about a £1 for a week’s subscription)

The population risk figures were my biggest concern with my 23andMe data. It’s understandable that an American company should tailor its product for the US market but very misleading to quote what are apparently statistics applicable to the US for customers in other countries:

For the record, the ancestry tests used by the Genographic Project, Family Tree DNA, Oxford Ancestors, etc do not for the most part look at SNPs. Instead they look at STR (short-tandem repeat) markers on the Y-chromosome and hypervariable regions 1 and sometimes 2 for the mtDNA test. No genes are involved. FTDNA’s Family Finder test does test SNPs but all the medically informative ones have been excluded and they provide no medical information to the consumer. They have been told by the FDA that their tests will not be affected.

If the FDA are indeed in the business of consumer protection then they are clearly not doing their job. It seems incredible that they have allowed a clearly fraudulent company like GeneWize to trade for at least two years without censure along with the other supplement companies who were shamefully not even named in the GAO report. Both 23andMe and Navigenics approached the FDA before they even set up their companies. Why didn’t the FDA work with the companies at the time to establish some common guidelines?